Ancient Glycans May Help Trace Human Evolution

Ancient DNA recovered from fossils is a valuable tool to study evolution and anthropology. Yet fossil DNA has not been found yet in any part of Africa, where it’s destroyed by extreme heat and humidity. In a potential first step at overcoming this hurdle, researchers at University of California San Diego School of Medicine and the Stony Brook University-affiliated Turkana Basin Institute. have discovered a new kind of glycan — a type of sugar chain — that survives even in a 4 million-year-old animal fossil from Kenya, under conditions where ancient DNA does not.

A partial upper jaw of Australopithecus anamensis recovered from the bone bed excavated at the site

While ancient fossils from hominins are not yet available for glycan analysis, this proof-of-concept study, published September 11, 2017 in Proceedings of the National Academy of Sciences, may set the stage for unprecedented explorations of human origins and diet.

“In recent decades, many new hominin fossils were discovered and considered to be the ancestors of humans,” said Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine at UC San Diego School of Medicine. “But it’s not possible that all gave rise to modern humans — it’s more likely that there were many human-like species over time, only one from which we descended. This new type of glycan we found may give us a better way to investigate which lineage is ours, as well as answer many other questions about our evolution, and our propensity to consume red meat.”

In their latest study, Varki and team found that, as part of its natural breakdown, a signature part of Neu5Gc is also incorporated into chondroitin sulfate (CS), an abundant component in bone. They detected this newly discovered molecule, called Gc-CS, in a variety of mammalian samples, including easily detectable amounts in chimpanzee bones and mouse tissues.

Meave Leakey

Like Neu5Gc, they found that human cells and serum have only trace amounts of Gc-CS — again, likely from red meat consumption. The researchers backed up that assumption with the finding that mice engineered to lack Neu5Gc and Gc-Cs (similar to humans) had detectable Gc-CS only when fed Neu5Gc-containing chow.

Curious to see how stable and long-lasting Gc-CS might be, Varki bought a relatively inexpensive 50,000-year-old cave bear fossil at a public fossil show and took it back to the lab. Despite its age, the fossil indeed contained Gc-CS.

That’s when Varki turned to a long-time collaborator — paleoanthropologist Meave Leakey, research professor in Stony Brook’s Department of Anthropology. Knowing that researchers need to make a very strong case before they are given precious ancient hominin fossil samples, even for DNA analysis, Leakey recommended that the researchers first prove their method by detecting Gc-CS in even older animal fossils. To that end, with the permission of the National Museums of Kenya, she gave them a fragment of a 4-million-year-old fossil from a buffalo-like animal recovered in the excavation of a bone bed at Allia Bay, on the east side of Lake Turkana. Hominin fossils were also recovered from the same horizon in this bone bed.

Leakey is hopeful about the role Gc-CS could play in the future, as an alternative to current approaches.

“Because DNA rapidly degrades in the tropics, genetic studies are not possible in fossils of human ancestors older than only a few thousand years,” she said. “Therefore such ancient glycan studies have the potential to provide a new and important method for the investigation of human origins.”

This research was funded, in part, by the National Institutes of Health and the Mathers Foundation of New York. The excavation of the Allia Bay bone bed was funded by the National Geographic Society.